This proposal is formulated to investigate the molecular mechanisms that specify some neural precursor cells to develop as oligodendrocytes, the myelinating cell type of the vertebrate central nervous system. The work takes advantage of transgenic zebrafish that express Green Fluorescent Protein under control of the olig2 promoter, which reveals neural precursors that produce oligodendrocytes and motor neurons. Specific Aim 1 is designed to identify all the types of cells that arise from precursors that express olig2 and to determine their lineage relationships, using a combination of transgenic reporter gone expression and in vivo cell labeling. Specific Aim 2 tests specific hypotheses concerning the role of Delta-Notch signaling in regulating cell fate decisions among olig2-expressing precursor cells using mutations and transgenic, conditional expression systems. Specific Aim 3 describes a genetic screen for mutations that modulate the number of oligodendrocytes in transgenic zebrafish embryos. This work will reveal new information concerning the gene functions that guide neural precursors to develop as oligodendrocytes, which may be utilized for therapies designed to treat diseased and injured nervous systems.